Serum and Lymphocytic Neurotrophins Profiles in Systemic Lupus Erythematosus: a Case-Control Study

Background

Neurotrophins play a central role in the development and maintenance of the nervous system. However, neurotrophins can also modulate B and T cell proliferation and activation, especially via autocrine loops. We hypothesized that both serum and lymphocytic neurotrophin levels may be deregulated in systemic Lupus erythematosus (SLE) and may reflect clinical symptoms of the disease.

Methods

Neurotrophins in the serum (ELISA tests) and lymphocytes (flow cytometry) were measured in 26 SLE patients and 26 control subjects. Th1 (interferon-γ) and Th2 (IL-10) profiles and serum concentration of BAFF were assessed by ELISA in the SLE and control subjects.

Findings

We have demonstrated that both NGF and BDNF serum levels are higher in SLE patients than healthy controls (p=0.003 and p<0.001), independently of Th1 or Th2 profiles. Enhanced serum NT-3 levels (p=0.003) were only found in severe lupus flares (i.e. SLEDAI ≥ 10) and significantly correlated with complement activation (decreased CH 50, Γ=-0.28, p=0.03). Furthermore, there was a negative correlation between serum NGF levels and the number of circulating T regulatory cells (Γ=0.48, p=0.01). In circulating B cells, production of both NGF and BDNF was greater in SLE patients than in healthy controls. In particular, the number of NGF-secreting B cells correlated with decreased complement levels (p=0.05). One month after SLE flare treatment, BDNF levels decreased; in contrast, NGF and NT-3 levels remained unchanged.

Conclusion

This study demonstrates that serum and B cell levels of both NGF and BDNF are increased in SLE, suggesting that the neurotrophin production pathway is deregulated in this disease. These results must be confirmed in a larger study with naive SLE patients, in order to avoid the potential confounding influence of prior immune-modulating treatments on neurotrophin levels.     

Trends in Prevalence of Overweight and Obesity in Danish Infants,Children and Adolescents – Are We Still on a Plateau?

Background

After the worldwide steep increase in child and adolescent overweight and obesity during the last decades, there is now evidence of a levelling off in the prevalence in many countries in the Western world.

Aim

To examine whether there still is a plateau in the prevalence of overweight and obesity in Danish children and adolescents, or whether the prevalence is decreasing or rising again.

Methods

The trends in the prevalence rates were based on three data sets providing comparable repeated estimates: 1) the Danish Health Visitors Child Health Database (DHVCHD) with measurements on infant and childhood height and weight from 2002 to 2011 (n up to 39,984), 2) the Danish National Birth Cohort (DNBC) with maternal reports of measured infant and childhood height and weight from 1998 to 2010 (n up to 56,826) and 3) the Danish part of the Health Behaviour in School-aged Children survey (HBSC) with self-reported information on adolescent height and weight from the years 2002 to 2010 (n = 16,557). Overweight and obesity were categorized according to WHO growth standards. Trends were assessed by repeated point estimates and linear regression analyses providing regression coefficients for changes in per cent per year with 95% confidence intervals (CI).

Results

The prevalence rates of overweight and obesity for infants, children and adolescents showed a mixed pattern of decline, stability and increase (ranging from -1.10 through 0.29 per cent per year with CI’s from -3.10 through 2.37). Overall, there were no consistent statistically significant trends upwards or downwards, although some significant downward trends in childhood and adolescence were observed.

Conclusion

This study, based on data from 1998 through 2011, showed that the prevalence rates of overweight and obesity among Danish infants, children and adolescents were largely still on a plateau with tendencies for a decline among children and adolescents.     

Urea Transporter UT-B Deletion Induces DNA Damage and Apoptosis in Mouse Bladder Urothelium

Background

Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line.

Methodology/Principal Findings

Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis.

Conclusions/Significance

UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.     

Whole Genome Sequencing of Field Isolates Reveals a Common Duplication of the Duffy Binding Protein Gene in Malagasy Plasmodium vivax Strains

Background

Plasmodium vivax is the most prevalent human malaria parasite, causing serious public health problems in malaria-endemic countries. Until recently the Duffy-negative blood group phenotype was considered to confer resistance to vivax malaria for most African ethnicities. We and others have reported that P. vivax strains in African countries from Madagascar to Mauritania display capacity to cause clinical vivax malaria in Duffy-negative people. New insights must now explain Duffy-independent P. vivax invasion of human erythrocytes.

Methods/Principal Findings

Through recent whole genome sequencing we obtained ≥70× coverage of the P. vivax genome from five field-isolates, resulting in ≥93% of the Sal I reference sequenced at coverage greater than 20×. Combined with sequences from one additional Malagasy field isolate and from five monkey-adapted strains, we describe here identification of DNA sequence rearrangements in the P. vivax genome, including discovery of a duplication of the P. vivax Duffy binding protein (PvDBP) gene. A survey of Malagasy patients infected with P. vivax showed that the PvDBP duplication was present in numerous locations in Madagascar and found in over 50% of infected patients evaluated. Extended geographic surveys showed that the PvDBP duplication was detected frequently in vivax patients living in East Africa and in some residents of non-African P. vivax-endemic countries. Additionally, the PvDBP duplication was observed in travelers seeking treatment of vivax malaria upon returning home. PvDBP duplication prevalence was highest in west-central Madagascar sites where the highest frequencies of P. vivax-infected, Duffy-negative people were reported.

Conclusions/Significance

The highly conserved nature of the sequence involved in the PvDBP duplication suggests that it has occurred in a recent evolutionary time frame. These data suggest that PvDBP, a merozoite surface protein involved in red cell adhesion is rapidly evolving, possibly in response to constraints imposed by erythrocyte Duffy negativity in some human populations.     

Intake of Farmed Atlantic Salmon Fed Soybean Oil Increases Insulin Resistance and Hepatic Lipid Accumulation in Mice

Background

To ensure sustainable aquaculture, fish derived raw materials are replaced by vegetable ingredients. Fatty acid composition and contaminant status of farmed Atlantic salmon (Salmo salar L.) are affected by the use of plant ingredients and a spillover effect on consumers is thus expected. Here we aimed to compare the effects of intake of Atlantic salmon fed fish oil (FO) with intake of Atlantic salmon fed a high proportion of vegetable oils (VOs) on development of insulin resistance and obesity in mice.

Methodology/principal findings

Atlantic salmon were fed diets where FO was partly (80%) replaced with three different VOs; rapeseed oil (RO), olive oil (OO) or soy bean oil (SO). Fillets from Atlantic salmon were subsequently used to prepare Western diets (WD) for a mouse feeding trial. Partial replacement of FO with VOs reduced the levels of polychlorinated biphenyls (PCB) and dichloro-diphenyl-tricloroethanes (DDT) with more than 50% in salmon fillets, in WDs containing the fillets, and in white adipose tissue from mice consuming the WDs. Replacement with VOs, SO in particular, lowered the n−3 polyunsaturated fatty acid (PUFA) content and increased n−6 PUFA levels in the salmon fillets, in the prepared WDs, and in red blood cells collected from mice consuming the WDs. Replacing FO with VO did not influence obesity development in the mice, but replacement of FO with RO improved glucose tolerance. Compared with WD-FO fed mice, feeding mice WD-SO containing lower PCB and DDT levels but high levels of linoleic acid (LA), exaggerated insulin resistance and increased accumulation of fat in the liver.

Conclusion/Significance

Replacement of FO with VOs in aqua feed for farmed salmon had markedly different spillover effects on metabolism in mice. Our results suggest that the content of LA in VOs may be a matter of concern that warrants further investigation.     

Assessing “Dangerous Climate Change”: Required Reduction of Carbon Emissions to Protect Young People,Future Generations and Nature

We assess climate impacts of global warming using ongoing observations and paleoclimate data. We use Earth’s measured energy imbalance, paleoclimate data, and simple representations of the global carbon cycle and temperature to define emission reductions needed to stabilize climate and avoid potentially disastrous impacts on today’s young people, future generations, and nature. A cumulative industrial-era limit of ∼500 GtC fossil fuel emissions and 100 GtC storage in the biosphere and soil would keep climate close to the Holocene range to which humanity and other species are adapted. Cumulative emissions of ∼1000 GtC, sometimes associated with 2°C global warming, would spur “slow” feedbacks and eventual warming of 3–4°C with disastrous consequences. Rapid emissions reduction is required to restore Earth’s energy balance and avoid ocean heat uptake that would practically guarantee irreversible effects. Continuation of high fossil fuel emissions, given current knowledge of the consequences, would be an act of extraordinary witting intergenerational injustice. Responsible policymaking requires a rising price on carbon emissions that would preclude emissions from most remaining coal and unconventional fossil fuels and phase down emissions from conventional fossil fuels.     

Mitochondrial targeting of recombinant RNAs modulates the level of a heteroplasmic mutation in human mitochondrial DNA associated with Kearns Sayre Syndrome

Mitochondrial mutations, an important cause of incurable human neuromuscular diseases, are mostly heteroplasmic: mutated mitochondrial DNA is present in cells simultaneously with wild-type genomes, the pathogenic threshold being generally >70% of mutant mtDNA. We studied whether heteroplasmy level could be decreased by specifically designed oligoribonucleotides, targeted into mitochondria by the pathway delivering RNA molecules in vivo. Using mitochondrially imported RNAs as vectors, we demonstrated that oligoribonucleotides complementary to mutant mtDNA region can specifically reduce the proportion of mtDNA bearing a large deletion associated with the Kearns Sayre Syndrome in cultured transmitochondrial cybrid cells. These findings may be relevant to developing of a new tool for therapy of mtDNA associated diseases.     

Seasonal plasticity of Ludwigia grandiflora under light and water depth gradients: An outdoor mesocosm experiment

Abiotic factors in the introduced area can limit the establishment of exotic species. Adaptation to new abiotic parameters through plastic responses is important for their establishment and distribution pattern. Survival and growth of exotic hydrophytes are related to their plasticity and their ability to adapt to local conditions. Light and water depth are two of the predominant factors determining survival, growth, distribution and abundance of aquatic plants. Although many studies have been carried out on the effect of water level and light on plant performance, their potential interactions are poorly understood. Here, we carried out an outdoor mesocosm experiment, in order to test the role of water depth, light intensity and their potential interactions on the growth and vigour of the invasive macrophyte species Ludwigia grandiflora. Three light intensities (100%, 70% and 50% of sunlight) and three water depths (30, 50 and 80 cm) were tested over a 6-week period, in spring, summer and autumn 2011. We showed that the mortality, biomass, apical and lateral growth of L. grandiflora, as well as its biomass allocation, varied according to the season and responded to both light intensity and water depth. Interactions between water depth and light intensity can have an amplifying effect on the growth of L. grandiflora. Similarities between shade and deep water adaptation responses were observed. A higher biomass and a high morphological plasticity in response to these factors were found particularly at the beginning of the life cycle. Although the invasive amphibious L. grandiflora shows a high tolerance to different water levels and light intensities, the optimal growth conditions for L. grandiflora in our experiment seem to be under full sunlight and in 30 cm of water. Colonization of light or low shade aquatic habitats, as well as shallow environments, can occur due to the high plasticity of L. grandiflora. These results may be important relative to increasing level of water bodies under climatic changes.     

Do stream fish track climate change? Assessing distribution shifts in recent decades

Understanding the ability of species to shift their distribution ranges in response to climate change is crucial for conservation biologists and resources managers. Although freshwater ecosystems include some of the most imperilled fauna worldwide, such range shifts have been poorly documented in streams and rivers and have never been compared to the current velocity of climate change. Based on national monitoring data, we examined the distributional changes of 32 stream fish species in France and quantified potential time lags in species responses, providing a unique opportunity to analyze range shifts over recent decades of warming in freshwater environments. A multi‐facetted approach, based on several range measures along spatial gradients, allowed us to quantify range shifts of numerous species across the whole hydrographic network between an initial period (1980–1992) and a contemporary one (2003–2009), and to contrast them to the rates of isotherm shift in elevation and stream distance. Our results highlight systematic species shifts towards higher elevation and upstream, with mean shifts in range centre of 13.7 m decade^?1 and 0.6 km decade^?1, respectively. Fish species displayed dispersal‐driven expansions along the altitudinal gradient at their upper range limit (61.5 m decade^?1), while substantial range contractions at the lower limit (6.3 km decade^?1) were documented for most species along the upstream–downstream gradient. Despite being consistent with the geographic variation in climate change velocities, these patterns reveal that the majority of stream fish have not shifted at a pace sufficient to track changing climate, in particular at their range centre where range shifts lag far behind expectation. Our study provides evidence that stream fish are currently responding to recent climate warming at a greater rate than many terrestrial organisms, although not as much as needed to cope with future climate modifications.     

Anthropogenic subsidies mitigate environmental variability for insular rodents

The exogenous input of nutrients and energy into island systems fuels a large array of consumers and drives bottom-up trophic cascades in island communities. The input of anthropogenic resources has increased on islands and particularly supplemented non-native consumers with extra resources. We test the hypothesis that the anthropogenic establishments of super-abundant gulls and invasive iceplants Carpobrotus spp. have both altered the dynamics of an introduced black rat Rattus rattus population. On Bagaud Island, two habitats have been substantially modified by the anthropogenic subsidies of gulls and iceplants, in contrast to the native Mediterranean scrubland with no anthropogenic inputs. Rats were trapped in all three habitats over two contrasting years of rainfall patterns to investigate: (1) the effect of anthropogenic subsidies on rat density, age-ratio and growth rates, and (2) the role of rainfall variability in modulating the effects of subsidies between years. We found that the growth rates of rats dwelling in the non-subsidized habitat varied with environmental fluctuation, whereas rats dwelling in the gull colony maintained high growth rates during both dry and rainy years. The presence of anthropogenic subsidies apparently mitigated environmental stress. Age ratio and rat density varied significantly and predictably among years, seasons, and habitats. While rat densities always peaked higher in the gull colony, especially after rat breeding in spring, higher captures of immature rats were recorded during the second year in all habitats, associated with higher rainfall. The potential for non-native rats to benefit from anthropogenic resources has important implications for the management of similar species on islands.